The role of serum factors in the initiation of DNA synthesis in cultured primary differentiated fetal rat liver cells which grow in a selective arginine deficient medium will be studied as a model for liver regeneration. This culture system will be used to study mechanisms that regulate the cell cycle through serum factors and nutrients, and to purify serum growth factors from rat serum and establish whether such molecules are involved in the initiation of liver cell growth in vivo after partial hepatectomy. Studies using quiescent Go arrested cultured hepatocytes are aimed at elucidating whether the stimulus for DNA synthesis initiation is present in sera of normal (NR) and partially hepatectomized (PH) rats although at different concentrations of whether a new serum factor is present in PH-serum but absent from NR-serum. Growing fetal rat liver cells can reversibly be arrested in Go when arginine is removed from the culture medium in the presence of dialyzed serum. Therefore, the role of serum factors in stimulating amino acid transport and their effect on phospholipid metabolism in the plasma membrane will be studied in quiescent cells and in different phases of the cell cycle. We will investigate whether serum dependent stimulation of ornithine decarboxylase is an essential requirement for initiation of DNA synthesis and whether polyamines are involved in the growth control in liver cells. The studies are aimed at understanding early effects of serum growth factors on the membrane structure (phospholipids) and its possible relation to increased arginine transport rates which lead to the initiation of DNA synthesis in primary fetal rat liver cells in culture.